The present invention relates to methods of peritoneal dialysis.
It is well known that all physiological liquids, e.g., blood and peritoneal fluid, accumulate and transport various toxins. These toxins are gradually processed by the liver and kidney. However, these organs are directly exposed to the action of toxins and their function may become impaired. It is therefore necessary to remove the toxins from the physiological liquids by treating them, e.g., in a special extracorporeal circuit. In the case of kidney and liver failure, it is especially important to provide efficient removal of toxic metabolic products.
A plurality of methods have been invented and have been utilized for removing toxins from blood or blood plasma. One of the most efficient such methods is dialysis. Dialysis, however is generally restricted to removing small toxic molecules, whereas so-called middle molecular weight toxins are eliminated inefficiently, even with more modern high-flux dialysis membranes.
It has been also proposed to remove toxins, both of small and larger size, with peritoneal solutions. A special solution, called peritoneal dialysate, is introduced into the peritoneal cavity through a permanent indwelling catheter placed in the abdominal wall. Dialysate in the amount of 2-3 liters fills the peritoneal cavity and dwells there for a period of time. During this period, intensive diffusion through the inner lining of the abdominal cavity (the peritoneal membrane) takes place under an osmotic pressure differential, so that components, including toxic ones, are exchanged between the microcirculation of the peritoneum and the dialysate fluid. Excess water, too, is removed from the body, when hyperosmotic dextrose (glucose) concentration in the dialysate solution is applied to effect the desired liquid transfer through the peritoneal membrane. Dialysate is drained from the peritoneal cavity thus removing excess water and dissolved toxic compounds.
Most peritoneal dialysis (PD) is performed as Continuous Ambulatory Peritoneal Dialysis (CAPD) where 3-4 exchanges of approximately 2 liters of fluid per exchange are preferred during the day and at night, with the dwell time of dialysate amounting up to 4-6 hours, and one 8-hour exchange overnight. It is also possible to use an automated fluid delivery system that performs the entire procedure automatically, as in Continuous Cyclic Peritoneal Dialysis (CCPD).
Water used to make the dialysate is ultrapure and is typically produced through reverse osmosis. The typical composition of dialysate is as follows:
After a single PD session is over, the spent fluid is discarded. With approximately 45,000 patients using PD every day in U.S. alone, the amount of PD fluid is significant. Another significant problem from an environment concern is the plastic containers that hold the fluid. Millions of these containers are discarded each year. Because of these problems, regeneration of the dialysate fluid and its reuse by reinfusing to the same patient is highly desirable. A feasible way would be to subject the dialysate fluid to purification, which removes, through a semi permeable membrane, excess water and small toxic molecules. This technique however, would have the same limitations that hemodialysis has, namely, that clearance of middle-size molecules, including several toxic proteins, through the membrane is slow and incomplete. Reusing the peritoneal dialysis fluid would thus result in the large toxic molecules to build up in the organism, which is characteristic of kidney failure patients on a permanent hemodialysis treatment.
Accordingly, it is an object of the present invention to provide a new method of peritoneal dialysis which is a further improvement of the existing methods.
In keeping with these objectives and with others which will become apparent hereinafter, one feature of the present invention resides, briefly stated, in a method of peritoneal dialysis which includes introducing dialysis solution into a peritoneal cavity; allowing the solution to dwell in the peritoneal cavity for a period of time to provide diffusion through an inner lining of an abdominal cavity with exchange of components between a microcirculation of a peritoneum and a dialysis fluid; withdrawing the dialysate from the peritoneal cavity, passing the spent dialysate with toxins through a material which has the size, shape, and structure selected so as to remove the toxins in a molecular range of 300-30,000 Dalton from the spent dialysis fluid; and returning the thusly purified peritoneal dialysis solution to the patient.
When the method is performed in accordance with the present invention, the reuse of the dialysis solution provides a significant economy of the peritoneal fluid. Discarding of the bags which accommodate the solution is drastically reduced.
Another advantage of reuse of the dialysate liquid is that, besides the toxic components that need to be removed, the liquid also contains large molecular weight proteins, first of all, albumin, that have been gradually released into the dialysate liquid through the peritoneal membrane during the dwelling period. These essential components of physiological liquids of the organism get los when the dialysate liquid is discarded, and the organism has to compensate for the loss by an intensified protein synthesis. If only small and middle size toxic species could be removed from the used dialysate, but not the albumin-type higher essential proteins, the reuse of the thus purified liquid would significantly reduce further migration and loss of these proteins with the dialysate liquid, due to a diminished concentration gradient between the dialysis liquid and the body tissue with respect to the above essential high molecular weight proteins.
In accordance with another feature of the present invention, the method further includes additionally passing the spent dialysis fluid with toxins along a dialysis membrane for removing excess water and small toxic molecules, before returning the spent and purified dialysate fluid to the patient.
In accordance with another feature of present invention, said passing includes passing the dialysis fluid through the material which is a porous hydrophobic polymer with an enhanced proportion of pores in a diameter range between 1 and 10 nm.
In accordance with a further feature of present invention, the porous hydrophobic polymer is a copolymer of a crosslinked divinyl compound selected from the group consisting of divinylbenzene and diisopropenylbenzene and a monovinyl compound selected from the group consisting of styrene, ethylstyrene, alkyl acrylate and acrylo nitrile.
In accordance with another feature of present invention the porous hydrophobic polymer includes a hypercrosslinked polystyrene prepared by post-crosslinking of a macroporous styrene-divinylbenzene copolymer swollen in a solvent.
Some materials of this type are disclosed in patent application Ser. Nos. 09/019,583 and 09/019,584.
In accordance with still another feature of the invention the withdrawn dialysis solution with toxins is passed along an ultrafiltration membrane with vacuum applied at opposite side, to remove excess water and partially small toxic molecules.
The novel features which are considered as characteristic for the present invention are set forth in particular in the appended claims. The invention itself, however, both as to its construction and its method of operation, together with additional objects and advantages thereof, will be best understood from the following description of specific embodiments when read in connection with the accompanying drawings.